Method and composition for improved anabolism

ABSTRACT

Nutritional compositions are provided containing at least one PPAR agonist, at least one PGC-1alpha agonist, and at least one creatine derivative. Methods of promoting anabolism and improving or enhancing physical performance using the compositions are provided. The compositions and methods can be combined with physical training or exercise.

This application claims the benefit of earlier filed U.S. ProvisionalPatent Application Ser. No. 61/259,633 filed on Nov. 9, 2009.

FIELD OF THE INVENTION

A composition that, through the stimulation of peroxisomeproliferator-activated receptors (PPARs) and peroxisomeproliferator-activated receptor-γ coactivator (PGC-1α) during training,regulates athletic function and stimulates the anabolic pathway isprovided. The composition may be utilized as a dietary supplement orconventional food to improve athletic function and/or muscle growth anddevelopment via improved anabolism.

BACKGROUND

Anabolism is a key factor in the process of muscle growth for athletesand body builders. Anabolism is comprised of multiple metabolicpathways, constructing larger molecules from their building blocks.Energy is a necessary part of these metabolic pathways. In contrast,catabolism is the deconstruction of large molecules into smaller ones.Anabolism is fueled by both the small molecules of catabolism as well asan energy source, such as, but not limited to, adenosine triphosphate(ATP). The anabolic process and related anabolic hormones stimulateprotein synthesis and muscle growth.

Anabolic reactions are synthesis reactions and are endergonic, meaningthat they consume more energy than they produce. Anabolism is theprocess of chemical reactions that combine simple molecules and monomersto form the body's complex structural and functional components. Glucosemay take part in or be formed via several anabolic reactions such as,for example, synthesis of glycogen or the synthesis of new glucosemolecules from byproducts of protein and lipid breakdown, i.e.,gluconeogenesis.

One way of promoting anabolism is through the use of a dietarysupplement or drug. However, many anabolic stimulation compositions areillegal or have been banned from use by athletes in a number ofprofessional, collegiate, and amateur sports. Additionally, anabolicstimulating products also generally tend to have undesired side effectsthat can be harmful to the health of an individual. Thus, there is aneed and a demand for a dietary ingredient or composition which canpromote anabolism without undesirable side effects and/or which issuitable for use by athletes.

For the most part, anabolism is increased where there is an energysource and a way to synthesize proteins and therefore build new muscle.One energy source is ATP. Alternative energy sources include compoundsor methods to increase metabolism. The ability and rate at which thebody can spare and replenish energy is critical for anabolism.

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptorprotein transcription factors that operate to regulate the expression ofgenes. PPARs have been identified in a wide variety of human tissue andplay an essential role in the regulation of processes such as cellulardifferentiation, development, and metabolism. The oral use ofingredients which increase the activity of PPARs is one approach tofostering anabolism and regulating athletic function.

Peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α(“PGC-1alpha”) regulates energy metabolism and promotes mitochondrialbiogenesis. Mitochondria convert nutrients into energy. While exercisealone is enough to increase the expression of PGC-1alpha, exercise plusknown activators of PGC-1alpha may work together to regulate energymetabolism and promote mitochondrial biogenesis, thereby stimulatinganabolism. The oral use of ingredients which affect the synthesis oractivity of PGC-1alpha in dietary supplements is another approach tofostering anabolism and regulating athletic function.

A transcription coactivator is defined as a protein or protein complexthat increases the probability of a gene being transcribed byinteracting with transcription factors but does not itself bind to DNAin a sequence-specific manner. The PPARs are members of a relativelylarge family of nuclear receptors, all of which are subject totranscriptional coactivation by PCG-1 alpha (Liang, et al., Advan.Physiol. Edu. (2006) 30:145-151).

In view of the above, there is a need and a desire for a dietarysupplement including or containing ingredients that help regulatePGC-1alpha and PPARs to foster anabolism and regulate athletic function.

SUMMARY OF THE INVENTION

The presently claimed invention relates to a method for the stimulationof anabolism and, more particularly, the administration to an individualof an effective amount of at least one compound that has an effect onPPAR and at least one compound which has an effect on PGC-1 alpha toenhance or increase anabolic processes in a human subject.

The object of the invention can be obtained, at least in part, byadministering to an individual (i.e., a human) a nutritional compositionincluding or containing ingredients that help regulate PGC-1alpha andPPARs to promote greater anabolism. The PGC-1alpha and PPAR regulatingsources can be administered alone or in conjunction with compounds thatpromote muscle formation, promote protein synthesis, stimulate themetabolism or help regulate other hormones that are essential toanabolism.

In accordance with one embodiment, the nutritional composition comprisesat least one PPAR agonist and at least one PGC-1alpha agonist.

In accordance with another embodiment, the nutritional compositionconsists essentially of at least one PPAR agonist and at least onePGC-1alpha agonist.

In a further embodiment, the nutritional composition consists of atleast one PPAR agonist and at least one PGC-1alpha agonist.

In a still further embodiment, the nutritional composition can comprise,consist essentially of, or consist of at least one compound that has aneffect on PPAR, PGC-1alpha, or both and at least one creatine derivativeor creatine containing compound.

In accordance with certain other embodiments, the nutritionalcomposition can further include central nervous system stimulants and/oran energy source to promote protein synthesis and/or increasemetabolism.

In accordance with other embodiments, a method for providing abeneficial physical effect can comprise administering to an individual(i.e., a human subject) a therapeutically effective amount of anutritional composition which comprises, consists essentially of orconsists of at least one PPAR agonist and at least one PGC-1alphaagonist. The beneficial physical effect can be improved, enhanced orincreased muscle growth, anabolism, anti-catabolism, strength, recovery,endurance, and/or mental focus, mood elevation, improved insulinresistance, increased nitric oxide production, and/or improved energymetabolism.

In accordance with further embodiments, a method for enhancing physicalperformance can comprise administering to an individual atherapeutically effective amount of a nutritional composition whichcomprises, consists essentially of or consists of at least one PPARagonist and at least one PGC-1alpha agonist. Enhanced physicalperformance includes, for example, improved or enhanced anabolism,anti-catabolism, anti-fatigue, strength, endurance, mental focus, and/orrecovery when combined with exercise.

The methods disclosed herein contemplate the administration of anutritional composition which can provide an improvement in anabolism incomparison to other pre-training, during-training, or post-trainingcompositions. Suitably, the nutritional compound promotes anabolismwithout unwanted and potentially dangerous side effects generallyassociated with other products, such as anabolic steroids, that promoteanabolism.

As used herein it is understood that the term “creatine containing” mayalso include derivatives and analogues of creatine and salts or estersthereof.

As used herein it is understood that the term “PGC-1” may includePGC-1α, PGC-1β, PGC-1δ and PGC-1γ. Also contemplated herein for use inthe nutritional compositions are PGC-1 agonists, antagonists, andderivatives, conjugates, and salts thereof.

As used herein it is understood that the term “PPAR” may include allperoxisome proliferator-activated receptors, and isoforms thereof. Alsocontemplated herein for use in the nutritional compositions are PPARagonists, antagonists, and derivatives, conjugates, and salts thereof.

DETAILED DESCRIPTION

Anabolism is comprised of multiple metabolic pathways, constructinglarger molecules from their building blocks. Energy is a necessary partof these metabolic pathways. In contrast, catabolism is thedeconstruction of large molecules into smaller ones. Anabolism is fueledby both the small molecules of catabolism as well as an energy source,such as, but not limited to, adenosine triphosphate (ATP). The anabolicprocess and related anabolic hormones stimulate protein synthesis andmuscle growth.

The object of the presently claimed invention can be obtained, at leastin part, by administering to an individual (i.e., a human subject) aneffective amount of a nutritional composition including one or moreingredients that help regulate PGC-1alpha and/or PPARs. The PGC-1alphaand PPAR regulating sources can be administered alone or in conjunctionwith compounds that promote muscle formation, promote protein synthesis,stimulate the metabolism, or regulate other hormones that are essentialto anabolism.

In accordance with one embodiment, a method for promoting anabolismincludes administering to an individual an effective amount of anutritional composition including PGC-1alpha and PPAR regulators. ThePGC-1alpha and PPAR regulating compounds act to induce activity of thePGC-1alpha and PPARs and are agonists.

PPARs are lipid-activated transcription factors that belong to thesteroid/thyroid/retinoic acid receptor superfamily. All of theircharacterized target genes encode proteins that participate in lipidhomeostasis. Certain PPARs induce the expression of many genes involvedin lipid anabolism. PPARs stimulate anabolic processes such asadipogenesis, lipogenesis and glucose uptake. PPARs also act asnutritional sensors that regulate a variety of homeostatic functionsincluding metabolism, inflammation and development. PPAR-gamma (PPAR-γ)regulates anabolism or storage. The equilibrium between anabolic andcatabolic processes is under the control of chondrocytes, which areunder the influence of PPARs. PPARs act by dimerizing with receptorsthat then bind to specific regulatory regions on the DNA of targetgenes, called peroxisome proliferator response elements (PPREs). Whenthe PPARs (and associated proteins in the PPRE complex) bind to thegenes, transcription of the target genes is then increased or decreased,depending on the gene. PPARs bind specific ligands and regulate genetranscription by binding to DNA, and can be activated by variouscompounds.

PGC-1alpha is a transcriptional coactivator of the PPARs that is thoughtto control adaptive responses to physiological stimuli. PGC-1alpha hasbeen shown to be upregulated with even a single bout of exercise. Thisincrease may play a role in mediating response to exercise, includingcardiovascular and metabolic responses. PGC-1alpha has been linked toadaptive thermogenesis, e.g., response to cold, and participates incarbohydrate and lipid metabolism. Fasting has been shown to increasethe activity of PGC-1alpha, while insulin has a suppressive effect onPGC-1alpha. PGC-1alpha has also been shown to prevent muscle damage bycertain chemical agents.

In accordance with certain embodiments the PPARs and/or the PGC-1alphacompounds or ingredients can be derived or obtained from a naturalsource such as, for example, a botanical or herbal source. Examples ofnatural sources of PPARs and/or PGC-1alpha activator compounds,components or ingredients include, but are not limited to, Epimediumsagittatum which is believed to promote PGC-1alpha, PPAR alpha (PPAR-α),and nuclear respiratory factor-1 (NRF-1) expression (i.e., act as anagonist), Epimedium grandiflorum which is believed to promote theexpression of PGC-1alpha, PPAR-alpha and NRF-1, and Japanese Knotweedwhich is believed to be a PGC-1alpha agonist. It is noted that the term“PPAR agonist” as used herein comprises naturally occurring botanicalsources that include PPAR activator compounds or components.

In accordance with certain other embodiments, the PPARs and/or thePGC-1alpha compounds or ingredients can be in the form of one or moreisolated, purified, or naturally-derived compounds such as, for example,resveratrol which is believed to be a PPAR agonist, piceatannol which isbelieved to be a PGC-1alpha agonist, sodium pyruvate which is believedto be a PGC-1alpha agonist, and phytanic acid which is believe to be aPPAR-α, PPAR-β, and PPAR-γagonist.

In accordance with certain embodiments, trans-resveratrol, resveratrolderivatives, and resveratrol-related compounds can be included in thenutritional composition as PPAR agonists and to promote or enhancerecovery after exercise. Resveratrol has been shown to have many healthbenefits, including as an anti-inflammatory, blood-sugar regulatory andmany cardiovascular benefits.

Piceatannol is the phenolic stilbenoid metabolite of trans-resveratrolwhich can be found in the seeds of the plant Euphorbia lagascae L.Piceatannol is also known as a natural analog of resveratrol and isbelieved to be a resveratrol precursor. Piceatannol is further believedto contribute to health benefits such as increased aerobic capacity,improved metabolic homeostasis, and/or improved insulin resistance.Piceatannol may work synergistically with creatine phytanate, phytanicacid, Japanese Knotweed, Rhodiola rosea, Epimedium grandiflorum,Epimedium sagittatum, and/or sodium pyruvate.

Japanese Knotweed (Polygonun cuspidatum) is an herbaceous plant that isa commercial source of resveratrol and is believed to be a PGC-1alphaagonist, an anti-inflammatory agent and acts as a selective estrogenreceptor modulator (SERM).

Phytanic acid is a branched-chain fatty acid that is derived from thephytanol side chain of chlorophyll. Phytanic acid is oxidized intopristanic acid. Phytanic acid is believed to be a PPAR-α, β and γagonist and is also believed to increase nitric oxide production.

In accordance with certain embodiments, the nutritional compositionincludes one or more PGC-1alpha and PPAR regulating compounds oringredients in combination with a source of creatine. Suitably, thecreatine sources may include salts, esters, derivatives, or conjugatesof creatine that further help induce activity of PGC-1alpha and PPARs,such as, for example, creatine heptyl ester, creatine ethyl ester, andthe like. Sources of creatine may include creatine salts that actsynergistically with other compounds in the invention. Heptanol,heptaminol and heptaminol precursors are contemplated which are anabolicand central nervous system stimulants, and may help increase musclemass. Another potential creatine source is creatine phytanate, which isbelieved to improve or enhance strength, endurance and/or muscle size.Other creatine containing salts, solvates, prodrugs, and conjugates arecontemplated as useful in the nutritional compositions. Useful creatinecontaining components include, but are not limited to, creatinemonohydrate, Creatine Alpha Amino-N-butyrate, Creatine EthylEster-Beta-Alanine intermixture, Creatinol-O-Phosphate-Malic AcidInterfusion complex, Sodium Creatine Phosphate Matrix, N-phosphatidylCreatine Heptanoate Ester, Creatine Heptanoate HCl, Ethyl2-[N-(1-(hexadecanamido)aminomethyl)-N-methylamino]acetate (reducedCreatine Palmitoyl Ethyl Ester HCl), and the like.

In accordance with further embodiments, the nutritional composition canalso include an energy source. One suitable energy source is sodiumpyruvate which is involved in the cycle that converts glucose to energy(i.e., the Krebs cycle). Enzymes of the Krebs cycle and electrontransport chain are located in the mitochondria and it is believed thatmitochondrial number and/or improved mitochondrial function may becentral to maintaining muscle integrity. Sodium pyruvate has been foundto increase the availability of ATP, improve work capacity, and act as aPGC-1alpha agonist. Sodium pyruvate has also been used to promote weightloss.

Another suitable energy source may be in the form of a powder, extractor preparation of Echeveria glauca, a succulent plant from theCrassulaceae family. Echeveria glauca is believed to increase energymetabolism and may also increase glycolytic enzyme production whichsupport anabolism. Another suitable energy source may be Panax gingsengand/or an extract thereof which contains or is enriched in ginsenocidesor ginsenosides, a class of steroid glycosides, and triterpene saponins,found exclusively in the plant genus Panax (ginseng).

The nutritional composition can further include one or more anabolicstimulants and/or central nervous system stimulants to help regulate theactivity of PPARs to promote anabolism and to act synergistically withother compounds. Examples of suitable anabolic and/or central nervoussystem stimulants include, but are not limited to hepatanol, heptaminol,L-lyxoflavin, Oxytropis muricata, hydroxyphenethylamine,N-benzoyl-2-hydroxyphenethylamine, andN-nicotinoyl-2-hydroxyphenethylamine.

Heptanol is a saturated primary aliphatic alcohol, also known as heptylalcohol. Heptanol is a heptaminol precursor, an anabolic and a centralnervous system stimulant, and can be found naturally in the carelessweed (Amaranthus palmeri) plant. Heptaminol is an amino alcohol that isalso classified as a vasodilator. Heptanol may work in synergy withcreatine heptyl ester or creatine ethyl ester to further promote theanabolic pathway.

L-lyxoflavin is a synthetic vitamin, which is similar to riboflavin(vitamin B2) except that the d-ribitol is replaced with d-lyxitol.L-lyxoflavin is a steroisomer of riboflavin that is derived from Lyxol.L-lyxoflavin promotes muscle accretion, increases the efficiency of feedutilization, increases growth rate, and is an anabolic vitamin analog.

Oxytropis muricata, hydroxyphenethalamine,N-benzoyl-2-hydroxyphenethylamine andN-nicotinoyl-2-hydroxyphenethylamine are beta-adrenoceptor agonists,anabolic and central nervous system stimulants which are believed tohelp increase or stimulate muscle growth.

Certain other beneficial compounds and/or natural botanicals, herbs oringredients may be added to the invention to act synergistically withkey ingredients to promote anabolism through the regulation of PPARs,such as PGC-1alpha, or to increase NO production, or for their healthbenefits. Such beneficial compounds and/or natural ingredients caninclude, but are not limited to: Rhodiola rosea, rosavin and/orsalidroside; Epimedium grandiflorum; Epimedium sagittatum and/oricariin; compounds and/or ingredients which promote protein synthesisand/or increased growth rate such as alpha-hydroxy-isovaleric acid,alpha-hydroxy-isocaproic acid, alpha-hydroxy-beta-valeric acid,Lespedine (kamferol-3,7-dirhamnoside), and/or Shilajit moomiyo extractwith fulvic acid and/or humic acid; compounds and/or ingredients whichare or contain antioxidants and/or promote improve muscle mass such askudzu powders, extracts or preparations, robinin, hyperin, and/orhawthorn powders, extracts or preparations; and compounds and/oringredients which promote insulin sensitivity such as loquat leafextract and/or maslinic acid.

Rhodiola rosea, a plant in the Crassulaceae family, is an adaptogen andis a natural herb that is known to increase a body's resistance tostress, trauma, anxiety and fatigue. The glycoside compounds Rosavin(s)and salidroside(s) are believed to be responsible for the antidepressantand anxiolytic actions of this plant. Rhodiola rosea is also thought toimprove exercise capacity, activate the synthesis of adenosinetriphosphate (ATP), act as an anti-inflammatory agent, reduce fatigueand is a PGC-1alpha agonist. Rhodiola rosea is generally used to reducerecovery time after intense workouts. In accordance with certainembodiments, Rhodiola rosea such as in the form of an extractstandardized for rosavins and/or salidorsides can be included in thenutritional composition as PPAR/PCG-1alpha agonists and/or as an energysource. In accordance with certain other embodiments, rosavin,salidroside, and/or an alternative botanical source of rosavin and/orsalidroside can be included in the nutritional composition.

Epimedium grandiflorum is an herbaceous flowering plant in the familyBerberidaceae. The active ingredient in Epimedium grandiflorum isicariin, which is known to increase nitric oxide. Epimedium grandiflorumis also believed to promote the expression of PGC-1alpha, PPAR-alpha andNRF-1.

Alpha-hydroxy-isovaleric acid, alpha-hydroxy-isocaproic acid andalpha-hydroxy-beta-methyl valeric acid are hydroxy acids. All threehydroxy acids have growth promoting capacity, increase protein synthesisand improve recovery time from exercise. Alpha-hydroxy amino acids mayalso have a standalone anabolic effect. Additional useful hydroxy acidsinclude alpha-hydroxy-gamma-methylthiobutyric acid,alpha-hydroxy-beta-phenylpropionic acid,alpha-hydroxy-beta-imidazolepropionic acid,alpha-hydroxy-beta-hydroxybutyric acid, alpha-hydroxy-gamma-aminocaproicacid, alpha-hydroxy-gamma-guanidinovaleric acid, and the like.

Epimedium sagittatum is an herbal treatment used to increase stamina.Epimedium sagittatum promotes PGC-1alpha, PPAR-alpha, and NRF-1expression, has antiosteoporotic effects and increases testosteronelevels. In accordance with certain embodiments, an Epimedium sagittatummaterial which has been standardized to include 10% icariin can beincluded in the nutritional composition. Additionally or alternatively,in accordance with certain other embodiments, icariin or anotherbotanical source of icariin can be included in the nutritionalcomposition.

Kudzu (Pueraria lobata) is a Japanese creeper associated with the legumefamily. In accordance with certain embodiments, a kudzu material whichhas been standardized to include 10% robinin can be included in thenutritional composition. Robinin has antioxidant properties and is ananabolic flavonoid. Kudzu materials are also believed to promoteincreases in muscle mass.

Loquat leaf extract is believed to improve insulin sensitivity, increaseprotein turnover rate, and stimulate growth. In accordance with certainembodiments, a loquat leaf extract which has been standardized for 10%maslinic acid can be included in the nutritional composition. Olive leafextract is believed to improve insulin sensitivity, increase proteinturnover rate, and stimulate growth. In accordance with certainembodiments, an olive leaf extract which has been standardized for 10%maslinic acid can be included in the nutritional composition.

Hawthorn (Crataegus monogyna) is a hedge plant in the rose family.Active compounds found in hawthorn materials include hyperin(hyperoside), an antioxidant, and various anabolic flavonoids. Hawthornis also known to be an anti-inflammatory agent and is suspected to helpincrease muscle mass. In accordance with certain embodiments, thenutritional supplement can include or contain a hawthorn material whichhas been standardized to include 10% hyperin (Hyperoside).

Shilajit moomiyo is an adaptogenic herb which can be used to enhancephysical and mental performance. Shilajit is believed to amplify thebenefits of other herbs by enhancing their bio-availability. Shilajit isalso believed to increase protein synthesis, growth rate and/or energyintake. Suitably, the nutritional composition can include a Shilajitmaterial or extract which has been standardized to include or contain10% humic acid and/or 10% fulvic acid. In accordance with certain otherembodiments, the nutritional composition can alternatively and/oradditionally contain fulvic acid, humic acid, and/or another botanical,natural, or herbal source of fulvic acid and/or humic acid.

The nutritional composition can further include one or more free aminoacids including essential amino acids and/or branched chain amino acids.Generally, it has been found that ingesting free amino acids has abeneficial impact on muscle performance and recovery and promotesanabolism. Essential amino acids have generally been shown to have bothan anti-catabolic effect and an anabolic effect during exercise and inthe post-exercise period while branched chain amino acids (BCAAs),particularly leucine, have been shown to preserve muscle and decreaseprotein breakdown during times of weight loss or other cataboliccircumstances.

Branched chain amino acids consumed during and post workout are thoughtto spare muscle glycogen, promote anabolism and anti-catabolism, promoterecovery, promote alanine and glutamine production, and regulate fatigue(lactic acid) and DOMS (Delayed Onset Muscle Soreness).

Free amino acids which can be utilized in the nutritional compositioninclude, but are not limited to, essential amino acids selected fromhistidine, methionine, phenylalanine, lysine, threonine, andcombinations thereof, and branched chain amino acids (BCAAs) selectedfrom isoleucine, leucine, valine, and combinations thereof, and/orsalts, analogues, esters, ethers, and derivatives thereof.

The essential amino acids histidine, methionine, threonine, lysine,phenylalanine, leucine, isoleucine, and valine are amino acids not madeby the body and must be consumed from food or supplements. Thenutritional composition and methods disclosed herein take full advantageof the ergogenic benefit of combining carbohydrates and essential aminoacids.

Additional components or compounds which can be utilized in thenutritional composition include: carbohydrates such as, for example,inulin and/or fructooligosaccharides; effervescent delivery agents suchas, for example, bicarbonate compounds; creatine transport aides and/orcreatine precursors such as, for example, guanidinopropionic acid,glycocyamine, and/or trimethylglycine (betaine); anti-fatigue agentssuch as, for example, beta-alanine, PEAK ATP® adenosine 5′ triphosphate(available from TSI Health Sciences, Inc. Missoula, Mont.), and/orcreatinol-O-phosphate; electrolytes such as, for example, glycerolstearate and additional sources of calcium, magnesium, potassium, and/orsodium; and excipients such as, for example, calcium silicate, malicacid, and/or citric acid.

The nutritional compositions disclosed herein can be administratedorally as an effective means of regulating athletic function. Inaddition to peroral use, other routes such as transdermal, sublingual,intranasal, or parenteral, can be used to effectively administer thedisclosed nutritional compositions. Other dosage forms and applicationsinclude capsules, tablets, caplets, liquids, beverages, liquid capsules,dissolvable films, powders, sprays or functional food products.

Solid nutritional compositions for oral administration in connectionwith a method for promoting anabolism during exercise may optionallycontain, in addition to the above enumerated nutritional compositioningredients or compounds: carrier materials such as corn starch,gelatin, acacia, microcrystalline cellulose, kaolin, dicalciumphosphate, calcium carbonate, sodium chloride, alginic acid, and thelike; disintegrators including, microcrystalline cellulose, alginicacid, and the like; binders including acacia, methylcellulose, sodiumcarboxymethylcellulose, polyvinylpyrrolidone, hydroxypropylmethylcellulose, ethyl cellulose, and the like; and lubricants such asmagnesium stearates, stearic acid, silicone fluid, talc, waxes, oils,colloidal silica, and the like. The usefulness of such excipients iswell known in the art.

Liquid nutritional compositions for oral administration in connectionwith a method for promoting anabolism during exercise can be prepared inwater or other aqueous vehicles. In addition to the above enumeratedingredients or compounds, liquid nutritional compositions can includesuspending agents such as, for example, methylcellulose, alginates,tragacanth, pectin, kelgin, carrageenan, acacia, polyvinylpyrrolidone,polyvinyl alcohol, and the like. The liquid nutritional compositions canbe in the form of a solution, emulsion, syrup, gel, or elixir includingor containing, together with the above enumerated ingredients orcompounds, wetting agents, sweeteners, and coloring and flavoringagents. Various liquid and powder nutritional compositions can beprepared by conventional methods.

As disclosed herein, a method for promoting anabolism during exerciseincludes orally administering to an individual engaged in exercise orphysical activity a nutritional composition comprising at least one PPARagonist and at least one PGC-1alpha agonist. The nutritional compositioncan additionally optionally include or contain one or more of: acreatine containing component; an anabolic stimulant; a central nervoussystem stimulant; a nitric oxide stimulant; an energy source or energyproducing agent; a compound that enhances or induces protein synthesis;an antioxidant; an agent to improve insulin sensitivity; and/orcompounds that enhance the bioavailability of other ingredients.

Oral daily doses of the nutritional composition can be between about 1to about 1000 grams, suitably between about 1 to about 100 grams, or,between about 1 to about 30 grams. One exemplary daily dosing schedulecan include one serving on training days. In another embodiment,multiple servings can be administered in a day if an individual engagesin multiple training sessions (i.e., one dose or serving can beadministered during each training session).

The nutritional composition and methods described above may be furtherunderstood in connection with the following Example.

EXAMPLE 1

In accordance with one embodiment, a serving of a nutritionalcomposition can optionally include or consist of the followingingredients:

TABLE 1 Ingredient Function Epimedium sagittatum standardized PPAR andfor 10% icariin PGC-1alpha Piceatannol Agonists Epimedium grandiflorumSodium pyruvate Japanese Knotweed trans-resveratrol Rhodiola roseaextract (root) (3% Rosavins and 1% Salidrosides) Pterostilbene(resveratrol analog) Creatine (including salt or solvate) Sources ofCreatine heptyl ester creatine Creatine ethyl esterCreatinol-O-Phosphate N-phosphatidyl creatine heptanoate ester Ethyl2-[N-1-(hexadecanamido)aminomethyl)-N- methylamino]acetate (reducedCreatine Palmitoyl Ethyl Ester HCl) Heptanol Anabolic and/or Heptaminolcentral nervous L-lyxoflavin system stimulants Oxytropis muricataHydroxyphenethylamine N-benzoyl-2-hydroxyphenethylamineN-nicotinoyl-2-hydroxyphenethylamine Echeveria glauca Energy sourcesSodium pyruvate Rhodiola rosea Panax gingseng (Acceleris ®)Alpha-hydroxy-isovaleric acid Protein synthesis/Alpha-hydroxy-isocaproic acid increased Alpha-hydroxy-beta-methylvaleric acid growth rate Alpha-Hydroxy-gamma-methylthiobutyric acidAlpha-Hydroxy-beta-phenylpropionic acidAlpha-Hydroxy-beta-imidazolepropionic acidAlpha-Hydroxy-beta-hydroxybutyric acid Alpha-Hydroxy-gamma-aminocaproicacid Alpha-Hydroxy-gamma-guanidinovaleric acid Shilajit moomiyo extractwith 10% fulvic acid and 10% humic acid Loquat leaf extract standardizedfor 10% maslinic acid Lespedine (kamferol-3,7-dirhamnoside) Kudzu(Pueraria lobata) standardized for 10% Antioxidant/ robinin improvesHawthorn (Crataegus monogyna) muscle mass standardized for 10% hyperinLespedine (kamferol-3,7-dirhamnoside) Loquat leaf extract standardizedfor 10% Improve insulin maslinic acid sensitivity

Acceleris® brand ginseng product is available from Unigen USA, Lacey,Wash.

The nutritional composition as in the above Example is prepared bymixing the components, i.e. chemical and botanical ingredients, inaqueous, lipid, or glycerol solutions. In addition, dried or powderformulations and/or tablets may be prepared. For example, a powderformulation would be an orally deliverable form, which would include theingredients listed in Table 1, and including a customized flavor system.For example, powder formulations for aqueous suspension arecontemplated. Thus, appropriate nutraceutical carriers and excipientscomprise liquid, solid, and powder formulations.

EXAMPLE 2

In accordance with an embodiment, it is expected that a human subjectusing the nutritional composition of Example 1 by oral administrationwill show an increase in anabolism after multiple days of use. Oneexpected measure of increased anabolism will be enhanced or increasedmuscle growth or size. It is also expected that a subject utilizing thenutritional composition of Example 1 will demonstrate enhanced physicalperformance and/or recovery from fatigue when combined with anestablished exercise regimen such as repetitive set weight lifting orweight training. One expected measure of enhanced physical performancewill be enhanced or increased muscle growth or size. It is expected thattotal work output will be increased in a subject administered thenutritional composition of Example 1 by oral administration aftermultiple days of use. Total work output, expressed in units of joulesper set, is measured as in U.S. Pat. No. 6,100,287, herein incorporatedby reference.

While in the foregoing specification this invention has been describedin relation to certain embodiments thereof, and many details have beenput forth for the purpose of illustration, it will be apparent to thoseskilled in the art that the invention is susceptible to additionalembodiments and that certain of the details described herein can bevaried considerably without departing from the basic principles of theinvention.

All references cited herein are incorporated by reference in theirentirety. The present invention may be embodied in other specific formswithout departing from the spirit or essential attributes thereof and,accordingly, reference should be made to the appended claims, ratherthan to the foregoing specification, as indicating the scope of theinvention.

1. A nutritional composition comprising: an amount of Epimediumsagittatum and phytanic acid effective to increase PPAR-alpha activity;an amount of Rhodiola rosea effective to increase PGC-1alpha activity;at least one creatine compound selected from the group consisting ofcreatine, creatine heptyl ester, creatine ethyl ester,creatinol-O-Phosphate, a salt thereof, and combinations thereof; and anutraceutically acceptable carrier, wherein the nutritional compositionstimulates anabolism in an individual.
 2. The nutritional composition ofclaim 1, further comprising at least one additional PPAR-alpha agonistselected from one or more of the group consisting of Epimediumgrandiflorum, sodium pyruvate, and combinations thereof.
 3. Thenutritional composition of claim 1, further comprising at least oneadditional PGC-1alpha agonist selected from the group consisting ofEpimedium grandiflorum, sodium pyruvate, piceatannol, and JapaneseKnotweed.
 4. The nutritional composition of claim 3, wherein the atleast one additional PPAR-alpha agonist and the at least one additionalPGC-1alpha agonist are the same component.
 5. The nutritionalcomposition of claim 1, further including at least one of a componentselected from the group consisting of heptanol, heptaminol,L-lyxoflavin, Oxytropis muricata, hydroxyphenethylamine,N-benzoyl-2-hydroxyphenethylamine, N-nicotinoyl-2-hydroxyphenethylamine,Echeveria glauca, Panax gingseng, alpha-hydroxyisovaleric acid,alpha-hydroxyisocaproic acid, alpha-hydroxy-beta-methyl valeric acid,alpha-hydroxy-gamma-methylthiobutyric acid,alpha-hydroxy-beta-phenylpropionic acid,alpha-hydroxy-beta-imidazolepropionic acid,alpha-hydroxy-beta-hydroxybutyric acid, alpha-hydroxy-gamma-aminocaproicacid, alpha-hydroxy-gamma-guanidinovaleric acid,kamferol-3,7-dirhamnoside, Shilajit moomiyo extract, Kudzu, Hawthorn,Loquat leaf extract, and mixtures thereof.
 6. A method for increasinganabolism in a human subject during physical activity, the methodcomprising administering to the subject an effective amount of anutritional composition according to claim
 1. 7. The method of claim 6,wherein the effective amount of the nutritional composition is a dailydose from about 1 gram to about 100 grams.
 8. The method of claim 6,wherein the nutritional composition further comprises at least one of acomponent selected from the group consisting of heptanol, heptaminol,L-lyxoflavin, Oxytropis muricata, hydroxyphenethylamine,N-benzoyl-2-hydroxyphenethylamine, N-nicotinoyl-2-hydroxyphenethylamine,Echeveria glauca, Rhodiola rosea, Panax gingseng,alpha-hydroxyisovaleric acid, alpha-hydroxyisocaproic acid,alpha-hydroxy-beta-methyl valeric acid,alpha-hydroxy-gamma-methylthiobutyric acid,alpha-hydroxy-beta-phenylpropionic acid,alpha-hydroxy-beta-imidazolepropionic acid,alpha-hydroxy-beta-hydroxybutyric acid, alpha-hydroxy-gamma-aminocaproicacid, alpha-hydroxy-gamma-guanidinovaleric acid,kamferol-3,7-dirhamnoside, Shilajit moomiyo extract, Kudzu, Hawthorn,Loquat leaf extract, and mixtures thereof.
 9. The method of claim 6,wherein said method increases total work output.
 10. The method of claim6, wherein said method increases muscle growth.